Plain DealerResearchers at University Hospitals Case Medical Center have found a natural body defense for possibly fighting C. diff.

CLEVELAND, Ohio -- Researchers at Case Western Reserve University have uncovered a natural defense mechanism that could be key to fighting the stubborn and sometimes deadly "superbug" Clostridium difficile, know as "C. diff," without using conventional antibiotics. The new findings were published Sunday in the online issue of the journal Nature Medicine.

C. diff, a bacterium resistant to many drugs, has become a major problem for hospital and nursing home patients in Ohio and nationwide killing more than 28,000 people each year, according to the Centers for Disease Control and Prevention.

Researcher Dr. Jonathan Stamler said in a phone interview last week that he and his colleagues have uncovered a natural defense produced in a person's body to fight C. diff.

C. diff often invades the colon after antibiotics have destroyed the healthy flora. The bacterium releases toxins in the gut that can cause diarrhea, more serious conditions such as colitis and sometimes death. Doctors often prescribe another antibiotic to fight C. diff, but the treatment doesn't always work.

Although human trials for the potential drug have not yet begun, Stamler said, there likely would be an alternative to antibiotics for treating C. diff. with fewer side affects.

In the study published in Nature Medicine, Stamler describes the mechanism that is capable of inactivating the toxins spread in the colon by C. diff.

Stamler explained that the newly discovered mechanism involves a nitric oxide-based molecule called S-nitrosoglutathione or GSNO. This molecule binds to the toxins secreted by C. diff, deactivates them and prevents them from penetrating and damaging cells.

The GSNO only binds when the toxin is doing damage, Stamler added.

GSNO works by inserting part of itself into the center of the toxin, he said, in a process called nitrosylation.

"Figuring out how the mechanism deactivates the toxins gives us a basis for developing new therapies that can directly target toxins and prevent bacterial infections from spreading," said Stamler, director of the Institute for Transformative Molecular Medicine at Case Western Reserve University and University Hospitals.

Stamler said he discovered the GSNO molecule and the nitrosylation mechanism for controlling protein function in previous research.

"It turns out," Stamler explained, "that the toxins secreted by C. diff are only turned on when they interact with another substance in the gut called InsP6," or nositolhexakisphosphate. This substance is commonly found in leafy vegetables and in the gastrointestinal tract.

The new research suggests that GSNO and S-nitrosylation, may have a universal function in protecting cells against microbial proteins, he said.

Investigators from the University of Texas in Galveston, University of California, Tufts University and the Commonwealth Medical College collaborated on the research.

C. diff has been a major concern in Ohio, which started a pilot study two years ago involving 60 hospitals, including some in the Cleveland area. It is spread by contact and seen mostly in those 65 and older with relapses in one-quarter of patients.

Preliminary findings of the Ohio study show that following guidelines on cleaning, hand washing and contact isolation have decreased the number of C. diff cases from 5,671 in 2008 to 4,861 in 2009, according to the Ohio Hospital Association. Hospital acquired C. diff can cost between $4,000 and $9,000 per patient to treat.

Stamler said that C. diff is a "massive public health problem that is rampant worldwide.

"No one really had any idea why some individuals would get C.diff and others would not," said Stamler. Some people seem to produce more of the toxin-fighting substances to ward off C. diff, he added.

"We should be able to give people GSNO-based drugs," he said, noting the goal of the continued research as it goes through the drug development process.

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